Endocytosis contributes to BMP2-induced Smad signalling and neuronal growth

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dc.contributor.authorHegarty, Shane V.
dc.contributor.authorSullivan, Aideen M.
dc.contributor.authorO'Keefe, Gerard W.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Councilen
dc.contributor.funderNational University of Irelanden
dc.date.accessioned2017-02-13T14:47:35Z
dc.date.available2017-02-13T14:47:35Z
dc.date.issued2017-02-08
dc.date.updated2017-02-13T14:37:32Z
dc.description.abstractBone morphogenetic protein 2 (BMP2) is a neurotrophic factor which induces the growth of midbrain dopaminergic (DA) neurons in vitro and in vivo, and its neurotrophic effects have been shown to be dependent on activation of BMP receptors (BMPRs) and Smad 1/5/8 signalling. However, the precise intracellular cascades that regulate BMP2-BMPR-Smad-signalling-induced neurite growth remain unknown. Endocytosis has been shown to regulate Smad 1/5/8 signalling and differentiation induced by BMPs. However, these studies were carried out in non-neural cells. Indeed, there are scant reports regarding the role of endocytosis in BMP-Smad signalling in neurons. To address this, and to further characterise the mechanisms regulating the neurotrophic effects of BMP2, the present study examined the role of dynamin-dependent endocytosis in BMP2-induced Smad signalling and neurite growth in the SH-SY5Y neuronal cell line. The activation, temporal kinetics and magnitude of Smad 1/5/8 signalling induced by BMP2 were significantly attenuated by dynasore-mediated inhibition of endocytosis in SH-SY5Y cells. Furthermore, BMP2-induced increases in neurite length and neurite branching in SH-SY5Y cells were significantly reduced following inhibition of dynamin-dependent endocytosis using dynasore. This study demonstrates that BMP2-induced Smad signalling and neurite growth is regulated by dynamin-dependent endocytosis in a model of human midbrain dopaminergic neurons.en
dc.description.sponsorshipIrish Research Council (R15897; SVH/AS/GOK); National University of Ireland (R16189; SVH/AS/GOK); Science Foundation Ireland (SFI under the Grant Number 15/CDA/13498)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHegarty, S. V., Sullivan, A. M. and O’Keeffe, G. W. (2017) 'Endocytosis contributes to BMP2-induced Smad signalling and neuronal growth', Neuroscience Letters, 643, pp. 32-37. doi:10.1016/j.neulet.2017.02.013en
dc.identifier.doi10.1016/j.neulet.2017.02.013
dc.identifier.endpage37
dc.identifier.issn0304-3940
dc.identifier.journaltitleNeuroscience Lettersen
dc.identifier.startpage32
dc.identifier.urihttps://hdl.handle.net/10468/3622
dc.identifier.volume643
dc.language.isoenen
dc.publisherElsevieren
dc.rights© 2017 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectEndocytosisen
dc.subjectBMP2en
dc.subjectDynamin-dependenten
dc.subjectSmad signallingen
dc.subjectNeurite growthen
dc.titleEndocytosis contributes to BMP2-induced Smad signalling and neuronal growthen
dc.typeArticle (peer-reviewed)en
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